PMID- 21520153
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20211020
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 71
IP  - 16
DP  - 2011 Dec
TI  - Active sonic hedgehog signaling between androgen independent human prostate 
      cancer cells and normal/benign but not cancer-associated prostate stromal cells.
PG  - 1711-22
LID - 10.1002/pros.21388 [doi]
AB  - BACKGROUND: Sonic hedgehog (Shh) signaling plays a pivotal role in 
      stromal-epithelial interaction during normal development but its role in 
      tumor-stromal interaction during carcinogenic progression is less well defined. 
      Since hormone refractory prostate cancer with bone metastasis is difficult to 
      treat, it is crucial to investigate how androgen independent (AI) human prostate 
      cancer cells communicate with their associated stroma. METHODS: Shh and its 
      target transcription factor, Gli1 mRNA, were assessed by RT-PCR and/or 
      quantitative RT-PCR in co-cultured cell recombinants comprised of AI C4-2 either 
      with NPF (prostate fibroblasts from normal/benign prostate gland) or CPF 
      (cancer-associated stromal fibroblasts) under Shh/cyclopamine (a hedgehog 
      signaling inhibitor) treatment. Human bone marrow stromal (HS27A) cells were used 
      as controls. In vivo investigation was performed by checking serum PSA and 
      immunohistochemical staining for the apoptosis-associated M30 gene in mice 
      bearing chimeric C4-2/NPF tumors. RESULTS: We found that (1) Shh has minimal 
      growth-stimulating effects on prostate cancer cells, but it stimulated the growth 
      of NPF but not CPF; (2) active Shh signaling was found between AI C4-2 cells and 
      NPF but not CPF; and (3) osteonectin (ON) is a Gli1 target gene in NPF and not in 
      CPF, and ON up-regulation in NPF can be blocked by cyclopamine CONCLUSIONS: Based 
      on co-culture and chimeric tumor models, active Shh-mediated signaling was 
      demonstrated between AI prostate cancer and NPF in a paracrine- and tumor 
      progression-dependent manner. Our study suggests that drugs like cyclopamine that 
      interfere with Shh signaling could be beneficial in preventing AI progression in 
      prostate cancer cells.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Shigemura, Katsumi
AU  - Shigemura K
AD  - Department of Urology, Winship Cancer Institute, Emory University School of 
      Medicine, Atlanta, Georgia, USA.
FAU - Huang, Wen-Chin
AU  - Huang WC
FAU - Li, Xiangyan
AU  - Li X
FAU - Zhau, Haiyen E
AU  - Zhau HE
FAU - Zhu, Guodong
AU  - Zhu G
FAU - Gotoh, Akinobu
AU  - Gotoh A
FAU - Fujisawa, Masato
AU  - Fujisawa M
FAU - Xie, Jingwu
AU  - Xie J
FAU - Marshall, Fray F
AU  - Marshall FF
FAU - Chung, Leland W K
AU  - Chung LW
LA  - eng
GR  - P01 CA098912/CA/NCI NIH HHS/United States
GR  - R01 CA122602/CA/NCI NIH HHS/United States
GR  - P01 CA98912/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110425
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Androgens)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (GLI1 protein, human)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (SHH protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Veratrum Alkaloids)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - ZH658AJ192 (cyclopamine)
SB  - IM
MH  - Androgens/metabolism
MH  - Animals
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Cell Communication/drug effects/physiology
MH  - Cell Line, Tumor
MH  - Chimera
MH  - Culture Media, Conditioned/metabolism
MH  - Fibroblasts/cytology/*metabolism
MH  - Hedgehog Proteins/genetics/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Paracrine Communication/drug effects/*physiology
MH  - Prostate/cytology/metabolism/pathology
MH  - Prostatic Neoplasms/drug therapy/*metabolism/pathology
MH  - Stromal Cells/cytology/*metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Veratrum Alkaloids/pharmacology
MH  - Zinc Finger Protein GLI1
PMC - PMC3680511
MID - NIHMS277886
EDAT- 2011/04/27 06:00
MHDA- 2011/12/14 06:00
PMCR- 2013/06/12
CRDT- 2011/04/27 06:00
PHST- 2010/03/24 00:00 [received]
PHST- 2011/03/01 00:00 [accepted]
PHST- 2011/04/27 06:00 [entrez]
PHST- 2011/04/27 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2013/06/12 00:00 [pmc-release]
AID - 10.1002/pros.21388 [doi]
PST - ppublish
SO  - Prostate. 2011 Dec;71(16):1711-22. doi: 10.1002/pros.21388. Epub 2011 Apr 25.